Vitamin D Supplementation

Rickets, sunlight and cod liver oil

A historical review in Pediatrics describes rickets as a common disease in seventeenth-century England, with Glisson's 1650 treatise giving a detailed clinical account. It states that the cause stayed elusive until the 1920s, with faulty diet, poor hygiene, lack of fresh air and sunshine, and lack of exercise each proposed during the late nineteenth and early twentieth centuries.

The same review credits animal experiments, folklore favoring cod-liver oil, and the geographic link between rickets and lack of sunshine in advancing understanding. It states that by the 1930s the discovery of vitamin D and the anti-rachitic properties of cod-liver oil made it possible to treat rickets and to eradicate it in the United States. Only the abstract of this review was read.

Fortification and the move toward testing

The NIH Office of Dietary Supplements (ODS) states that fortifying milk and other staples with vitamin D from the 1930s, together with cod liver oil, made rickets rare in the United States. It adds that the incidence of rickets is rising globally, including in the United States and Europe, especially among immigrants from African, Middle-Eastern and Asian countries.

Interest then widened beyond bone. A 2019 trial report notes that supplemental vitamin D, long prescribed for bone disorders, came to be viewed as a possible strategy against cancer and cardiovascular disease, and that routine vitamin D assessment and supplement use in US primary care had risen substantially. A 2018 review of case reports states that laboratory requests for vitamin D measurement increased more than 80-fold between 2000 and 2010.

Forms and the blood marker

The ODS describes vitamin D as a fat-soluble vitamin with two main forms in foods and supplements, D2 (ergocalciferol) and D3 (cholecalciferol), which differ chemically only in their side chains. Skin makes vitamin D on exposure to ultraviolet light. The vitamin is inactive until the liver converts it to 25-hydroxyvitamin D, also called calcidiol, and the kidney forms the active 1,25-dihydroxyvitamin D, or calcitriol. The marker discussed in guidelines is serum 25(OH)D.

This page covers D2 and D3 taken as supplements. A Cochrane review analyzed the related compounds calcitriol and alfacalcidol in a separate group of smaller trials, and findings for those compounds are not carried over here.

Deficiency, sufficiency and empiric supplementation

The ODS states that researchers have not definitively identified blood concentrations of 25(OH)D that mark deficiency, adequacy for bone health, or adequacy for overall health. It reports that a National Academies expert committee (the Institute of Medicine at the time) placed risk of deficiency below 30 nmol/L (12 ng/mL), possible inadequacy at 30 to 50 nmol/L, sufficiency for most people at 50 nmol/L (20 ng/mL) or more, and possible adverse effects above 125 nmol/L (50 ng/mL).

The US Preventive Services Task Force notes that no one serum cutpoint defines deficiency and that no consensus exists on levels representing optimal health. The 2024 Endocrine Society guideline defines empiric supplementation as vitamin D intake that exceeds the Dietary Reference Intakes and is implemented without testing 25(OH)D, which separates it from treating established deficiency.

Supplement forms and related pages

Vitamin D is naturally present in a few foods, added to others, and sold as a dietary supplement, alone or with calcium. This page is a member of the Machipedia family page Dietary Supplements, which covers supplements as a category and is not repeated here. Related Machipedia pages include Nutritional Therapy and Dietetics, which cover food-based advice, and Magnesium Supplementation and Collagen Supplements, which cover other single-ingredient supplements.

Blood testing

The ODS reports that vitamin D status testing has become a more common part of routine blood work ordered in US primary care, irrespective of indications, and that no studies have examined whether screening improves health outcomes. This page does not describe how tests are ordered or interpreted for individuals.

Who gives advice

In the United Kingdom, the NHS states that government advice is for everyone to consider a daily supplement in autumn and winter, that supplements are sold at most pharmacies and supermarkets, and that qualifying women and children can get free supplements through the Healthy Start scheme. NICE guidance addresses commissioners, public health teams and health professionals, and calls for health professionals in contact with at-risk groups to recommend supplements. No practitioner register or training standard specific to vitamin D supplementation was found in the sources reviewed.

Established uses: rickets and osteomalacia

The ODS states that vitamin D deficiency can appear as rickets in children, with soft bones and skeletal deformities, and as osteomalacia in adolescents and adults, and that prolonged exclusive breastfeeding without vitamin D supplementation can cause rickets in infants. The 2024 Endocrine Society guideline suggests empiric supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets.

Broader claimed uses

Supplements are also promoted for cancer, cardiovascular disease, diabetes, infections and COVID-19. The VITAL investigators describe the basis as ecologic and laboratory findings and observational links between low 25(OH)D and disease, noting that such results cannot establish causality. The NHS states that there is not enough evidence to support taking vitamin D solely to prevent or treat COVID-19.

Groups named as higher risk of deficiency

The ODS lists breastfed infants, older adults, people with limited sun exposure, people with dark skin, people with conditions limiting fat absorption, and people with obesity or gastric bypass surgery. The NHS names people who are rarely outdoors, those in care homes, those who cover most of their skin outdoors, and people with dark skin, and NICE adds pregnant and breastfeeding women. The ODS notes that whether lower levels in people with dark skin carry health consequences is not clear.

Bone health, falls and fractures

A Cochrane review (53 trials, 91,791 participants; searches to December 2012) found high-quality evidence that vitamin D alone is unlikely to prevent hip fracture (risk ratio 1.12, 95% CI 0.98 to 1.29), while vitamin D plus calcium slightly reduced hip fracture (0.84, 0.74 to 0.96). The USPSTF recommended against low-dose vitamin D and calcium for fracture prevention in community-dwelling postmenopausal women and found insufficient evidence for higher amounts; this excludes people with osteoporosis, vitamin D deficiency or high fall risk.

The ODS reports that the Task Force found with moderate certainty that vitamin D does not reduce falls in community-dwelling older adults. In DO-HEALTH (1,488 adults aged 70 or older), vitamin D3 did not reduce vertebral fractures, and ViDA reported no effect on non-vertebral fractures or falls.

Cancer, heart disease and diabetes

VITAL randomized 25,871 US adults; over a median 5.3 years vitamin D did not reduce invasive cancer (hazard ratio 0.96, 95% CI 0.88 to 1.06) or major cardiovascular events (0.97, 0.85 to 1.12), with no excess hypercalcemia. D2d randomized 2,423 adults with prediabetes; diabetes occurred less often with vitamin D but not significantly (0.88, 0.75 to 1.04; median follow-up 2.5 years). ViDA (5,110 adults) reported no effect on its main outcomes and suggested future research in deficient people.

Respiratory infections and COVID-19

A BMJ individual-participant meta-analysis of 25 trials (11,321 participants) found a lower odds of acute respiratory infection (adjusted odds ratio 0.88, 0.81 to 0.96), with larger effects with daily or weekly use and baseline 25(OH)D below 25 nmol/L. A Cochrane living review of COVID-19 treatment found three trials (356 participants) and judged the evidence very uncertain.

Institute of Medicine and Endocrine Society, 2011

The ODS reports that the Institute of Medicine committee found the evidence inadequate or too contradictory to conclude that vitamin D affects outcomes other than bone health. The 2011 Endocrine Society guideline suggested measuring serum 25(OH)D in patients at risk of deficiency, and found insufficient evidence to recommend screening people not at risk or prescribing vitamin D for cardiovascular protection.

Endocrine Society, 2024

The 2024 guideline suggests empiric supplementation for ages 1 to 18, adults aged 75 or older, pregnancy and high-risk prediabetes, and against supplementation above the Dietary Reference Intakes in healthy adults under 75. It found no trial evidence supporting routine 25(OH)D testing and no clear target level, and suggests against routine testing in all populations considered. Its supporting review found that high-dose intermittent use may increase falls.

USPSTF and the threshold dispute

In 2021 the USPSTF issued an I statement, finding current evidence insufficient to assess the balance of benefits and harms of screening asymptomatic adults. The ODS attributes differences among national and professional guidelines to incomplete understanding of the biology and to differing purposes, and notes that many studies used unstandardized 25(OH)D assays, which can limit conclusions.

Toxicity and hypercalcemia

The ODS states that vitamin D toxicity causes hypercalcemia, hypercalciuria and high 25(OH)D, and in extreme cases kidney failure, soft-tissue calcification, arrhythmia and death, and that toxicity is almost always due to excessive supplement intake. It lists Tolerable Upper Intake Levels from 25 to 100 mcg by age, set by the National Academies in 2010.

A review of 13 published cases found severe intoxication, with serum 25(OH)D between 150 and 1,220 ng/mL and calcium between 11.1 and 23.1 mg/dL, caused by manufacturing errors, patient overdosing or prescriber error. The Cochrane fracture review found hypercalcemia, usually mild, more common with vitamin D (risk ratio 2.28).

Kidney stones and interactions

The USPSTF found adequate evidence that vitamin D with calcium increases kidney stones, while the ODS notes that shorter trials of vitamin D alone found more hypercalcemia but not stones. The ODS names orlistat, statins, corticosteroids and thiazide diuretics as medicines that interact with vitamin D or affect its levels.

Care boundaries

The Cochrane plain-language summary advises that people with kidney stones, kidney disease, high blood calcium, gastrointestinal disease or heart disease risk seek medical advice before taking vitamin D with calcium. Supplements are not described by these sources as a replacement for medical diagnosis or treatment of rickets, osteomalacia or osteoporosis.